Studies were performed which precisely delineated the immunological defects in AIDS. Patients manifest a total lymphocytopenia with a selective quantitative deficiency in the helper/inducer subset of T lymphocytes phenotypically defined by OKT4 or Leu 3 monoclonal antibodies. Of particular note was the finding that the OKT4 subset of cells was also found to be qualitatively defective in that they manifested a profound deficiency in inducer/helper function. Although the OKT8 subset of T cells from AIDS patients functioned normally as suppressor cells when provided with a source of normal T4 cells, they were in an abnormally activated state expressing the Ia and T10 antigens characteristic of activated T cells. The selective quantitative and qualitative defect in OKT4 cells is compatible with one of the potential etiologies of AIDS which is an infection of OKT4 cells with a lymphocytotropic virus such as a retrovirus. AIDS patients also manifest a defect in natural killer (NK) cell activity as well as cell-mediated cytotoxicity against cytomegalovirus-infected target cells. Of particular note was the finding that in vitro incubation of AIDS lymphocytes with interleukin 2 (IL2) resulted in a dramatic normalization of the NK cell as well as the cytotoxic responses against viral infected target cells. This served as the basis for the institution of a trial of in vivo IL2 administration to AIDS patients in an attempt to at least partially reconstitute their defective immune function. AIDS patients were also shown to be defective in their cell-mediated and humoral immune response to in vivo immunization with soluble antigens such as keyhole limpet hemocyanin (KLH). Furthermore, their lymphocytes did not respond in vitro to KLH stimulation with either a blastogenic or antibody response. Finally, we demonstrated a profound defect of B cell function in AIDS patients. Their B cells are profoundly activated in vivo such that they are virtually all in the activated state, strongly suggesting that they are responding in an abnormal fashion to an antigenic (probably viral) stimulus in the absence of adequate T cell control. Secondary to this abnormal in vivo B cell activation is a defect in the ability of these cells to be triggered in vitro by an activation signal.